Breast cancer arises from estrogen-responsive breast epithelial cells. Estrogen activity is thought to promote the development of breast cancer, and many breast cancers are initially dependent on estrogen at the time of diagnosis. Anti-estrogen compositions have therefore been used to treat breast cancer.
A frequent mechanism of increased gene expression in human cancers is amplification, i.e., the copy number of a DNA sequence is increased, in a cancer cell compared to a non-cancerous cell. In breast cancer, commonly amplified regions are derived from 17q21, 8q24, and 11q13 which encode erbB-2, c-myc, and cyclic D1 respectively (Devilee et al., 1994, Crit. Rev. Oncog. 5:247–270). Recently, molecular cytogenetic studies have revealed the occurrence in breast cancers of additional regions of increased DNA copy number (Isola et al., Am. J. Pathol. 147:905–911, 1995; Kallioniemi et al., Proc. Natl. Acad. Sci. USA 91:2156–2160, 1994; Muleris et al., Genes Chromo. Cancer 10:160–170, 1994; Tanner et al., Cancer Research 54:4257–4260, 1994; Guan et al., Nat. Genet. 8:155–161, 1994).
Breast cancer is the second leading cause of cancer deaths in American women, and it is estimated that an American woman has at least a 10% cumulative lifetime risk of developing this disease. Early diagnosis is an important factor in breast cancer prognosis and affects not only survival rate, but the range of therapeutic options available to the patient. For instance, if diagnosed early, a “lumpectomy” may be performed, whereas later diagnosis tends to be associated with more invasive and traumatic surgical treatments such as radical mastectomy. The treatment of other cancers likewise is benefitted by early diagnosis, for instance the prognosis in the treatment of lung cancer, colorectal cancer and prostate cancers is greatly improved by early diagnosis. There is a need for a simple and reliable method of diagnosis of cancers in general and of breast cancer in particular. There is a need for a method of screening for compounds that inhibit the interaction between an estrogen receptor ER and an ER-dependent nuclear receptor co-activator molecule in order to identify molecules useful in research diagnosis and treatment of cancer. There is also a need for a method for identifying tamoxifen-sensitive cancer patients in order to better manage treatment. A solution to these needs would improve cancer treatment and research and would save lives.